Traditionally, hematological studies have relied upon morphologic and histochemical techniques except in the case of the reticulocyte which has been annnnfavorite target for studies of gene structure and function by recombinant DNA techniques. We propose a system in which recombinant DNA techniques can be used to study the much more complex series of differentiation steps leading from pormyelocytes to either granulocytes or macrophages. Using an "immortal" human leukemic cell line which can be induced to differeniate in vitro, we have already constructed libraries of clones of genes expressed at diferent developmental stages of acute myeloid leukemia. Many genes which are strongly regulated have been isolated. The system has a unique set of advantages for the discovery of what control signals are active during hematopoietic differentiation and the direct relation of their structure and function. In addition, the regulated genes we have identified will be used to classify human leukemias according to their expression of particular gene sequences. We will make the appropriate correlations between such a classification and traditional morphology, histochemistry, response to treatment and the natural history of leukemia in each patient. We hope to identify gene products whose expression in particular leukemias will serve as useful diagnostic probes for choosing and guiding the optimal therapy.